Therapeutic benefits can be achieved in some instances by providing a bioactive agent to a specific target tissue, instead of systemically. This is because the effect of the agent on the target tissue can be maximized while the side effects on other tissues can be minimized. Therapeutic benefits can also be achieved by providing a bioactive agent to a subject in a manner that provides controlled release of the bioactive agent. Controlled release of a bioactive agent can allow the concentration of the bioactive agent at the target tissue site to remain at a more consistent therapeutic level.
One technique for providing controlled-release site-specific drug delivery is to use a bioactive agent-eluting coating system disposed on a medical device. The coating can serve to control the rate at which the bioactive agent is eluted. In addition, because the coating is disposed on a medical device and because the medical device can be positioned as desired within the body of a patient, the delivery of the bioactive agent can be site-specific.
However, some types of bioactive agents may degrade or otherwise lose their activity if they are exposed to solvents used to apply coatings onto a substrate. In addition, some coating systems may not provide desired elution rate control of specific bioactive agents.
Accordingly, there is a need for polymeric matrices and their preparation, such as coatings, that can preserve the activity of bioactive agents. There is also a need for polymeric matrices that can provide elution rate control of bioactive agents as desired.
Some bioactive agents, such as proteins, exhibit activity that depends on their tertiary structure. Tertiary structure can be influenced by various factors external to the bioactive agent itself including temperature, solvent, other solutes, accessory molecules (such as chaperonins) and the like. Therefore, bioactive agent activity can inadvertently be degraded or even eliminated as a result of the handling conditions the bioactive agent is subjected to.
The process of putting a bioactive agent into a matrix forming solution and then disposing that solution upon a substrate (for example, by spraying) can involve exposure to a variety of solvents, exposure to other molecules, and exposure to varying temperatures. Because of their potential effect on the tertiary structure of a molecule, all of these conditions can potentially adversely affect the activity of the bioactive agent.
One approach to protecting the activity of a bioactive agent is to formulate it as a microparticle. As a microparticle, the bioactive agent can be protected during the process of dispersing it in a polymeric solution and applying it on to a substrate.